Publications [#327282] of David B. Dunson

Papers Published

  1. Moffitt, AB; Ondrejka, SL; McKinney, M; Rempel, RE; Goodlad, JR; Teh, CH; Leppa, S; Mannisto, S; Kovanen, PE; Tse, E; Au-Yeung, RKH; Kwong, Y-L; Srivastava, G; Iqbal, J; Yu, J; Naresh, K; Villa, D; Gascoyne, RD; Said, J; Czader, MB; Chadburn, A; Richards, KL; Rajagopalan, D; Davis, NS; Smith, EC; Palus, BC; Tzeng, TJ; Healy, JA; Lugar, PL; Datta, J; Love, C; Levy, S; Dunson, DB; Zhuang, Y; Hsi, ED; Dave, SS, Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2., The Journal of Experimental Medicine, vol. 214 no. 5 (May, 2017), pp. 1371-1386
    (last updated on 2017/12/16)

    Abstract:
    Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.